DDR1 associates with TRPV4 in cell‐matrix adhesions to enable calcium‐regulated myosin activity and collagen compaction

Tissue fibrosis manifests as excessive deposition of compacted, highly aligned collagen fibrils, which interfere with organ structure and function. Cells in collagen‐rich lesions often exhibit marked overexpression of discoidin domain receptor 1 (DDR1), which is linked to increased collagen compaction through the association of DDR1 with the Ca2+‐dependent nonmuscle myosin IIA (NMIIA). We examined the functional relationship between DDR1 and the transient receptor potential vanilloid type 4 (TRPV4) channel, a Ca2+‐permeable ion channel that is implicated in collagen compaction. Fibroblasts expressing high levels of DDR1 were used to model cells in lesions with collagen compaction. In these cells, the expression of the β1 integrin was deleted to simplify studies of DDR1 function. Compared with DDR1 wild‐type cells, high DDR1 expression was associated with increased Ca2+ influx through TRPV4, enrichment of TRPV4 in collagen adhesions, and enhanced contractile activity mediated by NMIIA. At cell adhesion sites to collagen, DDR1 associated with TRPV4, which enhanced DDR1‐mediated collagen alignment and compaction. We conclude that DDR1 regulates Ca2+ influx through the TRPV4 channel to promote critical, DDR1‐mediated processes that are important in lesions with collagen compaction and alignment.

• Publication year

  2022

• Venue

  Journal of Cellular Physiology

• Publication date

  2022-02-12

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1002/jcp.30696PMID 35150133
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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